1. Master Batch Record Approvals Name Signature Date Originator

Transcription

1 Effective: Page 1 of Master Approvals Name Signature Date Originator Ravikanth Kona Production Ravikanth Kona Quality Control Seon Hepburn Stephen Hoag Quality Assurance 2. Product Details Description Fexo A- Fexofenadine Hydrochloride 60 mg Tablets HPC: 5%; Inlet temp: 50 0 C; Compression force: 5 kn Part No. F-7046 Batch Quantity Storage Conditions Batch size: 350 gm. Approx No. tablets: Ambient - conditions, store in tight container protected from light and moisture 3. Production Issuance Issued By Issuer has reviewed the to ensure that the copy is a complete, accurate copy of the Master. Stephen W. Hoag (Print) Issued By Quality Assurance Signature Date Issued To Production has reviewed the to ensure that the copy is a complete and correct. Production is responsible for the following issuance. Ravikanth Kona (Print) Issued To - Production Signature Date

2 Effective: Page 2 of Signature and Training Log All personnel making entries on this must complete the Signature Log. Completion of the Signature Log indicates that each person has been thoroughly trained on this and all documents listed in Section 5: Reference Documentation. Note: The Signature Log completion does not supersede the requirements of GMP Training Program (SOP-006). Name Signature Initials Date Ravikanth Kona Stephen W. Hoag 5. Reference Documentation SOP-003: Good Documentation Practices SOP-006: GMP Training Program SOP-005: Nonconformances SOP-009: Material Storage and Inventory Procedure SOP-011: Facility Cleaning Procedures SOP-012: Temperature and Humidity Monitoring SOP-015: Gowning Procedures SOP-017: Retain Sample Program SOP-019: Material weighing and Dispensing SOP-020: Equipment Calibration SOP-021: s SOP-025: B2 Stokes tablet press SOP-0 SOP-0 : V- blender : Fluid bed

3 Effective: Page 3 of Bill Of Materials Description Part Number Quantity Req d Lot No. Qty Staged Exp / Retest QA Verified Fexofenadine Hydrochloride R-1057 CI Avicel PH 102 (Microcrystalli ne cellulose) Klucel EXF (Hydroxyprop yl cellulose) Lactose monohydrate 110M Mg Stearate - Kosher Passover (Covidien) Kollidon K-30 (Polyvinyl pyrollydone) Ac-Di-Sol (Croscarmell ose Na) Aerosil 200 (Aerosilized silica) R-1002 P R R R-1017 K22610 R-1013 G10976P T0 R-1016 P R Sterile water R-1038

4 Effective: Page 4 of Processing Equipment Equipment Description ID No. Previous Cal. Cal. Req d By QA Verified Fluid bed (Fluid Air model # 0002) UMB- B2-Stokes tablet press UMB /26/2010 Meets requirement UMB internal calibration Balance OHAUS CD 33 Check wt. wt. = wt. = wt. = Balance Mettler PC 440 Check wt. wt. = wt. = wt. = V- blender (Kelly Patterson) UMB- 02/23/2012 Meets requirement Mes. Wt. Toler ±0.1% Check at least 3 wts in the range to be measured UMB- 02/23/2012 Meets requirement Mes. Wt. UMB- Toler ±0.1% Check at least 3 wts in the range to be measured Meets requirement Stanley (American Scale & Equipment co Inc) If tolerance outside 0.1% range call QA Stanley (American Scale & Equipment co Inc) If tolerance outside 0.1% range call QA UMB internal calibration Timer VWR Model# UMB calibration expires 10/17/2013 Meets requirement Control Company

5 Effective: Page 5 of 17 Sieve (Cole Palmer) sizes 18 and 30 Masterflex precision pump tubing ( ) Mettler Toledo LOD equipment NA NA NA NA NA NA NA NA NA NA NA NA 8. Area Clearance Step 1. GMP Processing Area(s): Room: 2. Review the GMP Processing Area Logbook(s) and ensure that the Logbook(s) is (are) complete, and up-to-date. 3. Review all applicable GMP Processing Area Logbook(s) and verify that Cleaning and Sanitization has been performed according to Facility Cleaning Procedures (SOP-011), and that the Cleaning and Sanitizing occurred within the allowed time before a GMP operation. Date Cleaning Complete: Date Sanitizing Complete: 4. Verify that all work surfaces within the GMP Processing Area have been Sanitized (e.g., wiped with NLT 70% Isopropanol) on the day of production. Verify that this Sanitization has been recorded in the Logbook(s). 5. Review Section 6: Bill of Materials, and ensure that it is complete, accurate, and that all necessary materials are present for the GMP operation. Ensure that all GMP Materials are Released, Approved and have sufficient time to the Use By Date. QA Verified

6 Effective: Page 6 of Review Section 7: Processing Equipment, and ensure that it is complete, accurate, and that all necessary equipment is present, cleaned and calibrated, as appropriate. Review the Logbook for each piece of GMP Equipment, and ensure that the Logbooks are correctly filled out. Fluid bed (UMB-00 Twin shell blender (UMB-00 ) - ) B2-Stokes tablet press (UMB-0013) 7. Verify that the cgmp Processing Area does not contain any items from previous batches or cleaning activities and that no items unrelated to the current cgmp batch are present. 8. Area Clearance Complete. QA shall Complete the Area Clearance Sign (SOP-021, Attachment 1) and affix it to the GMP Processing Area entrance.

7 Effective: Page 7 of Weigh the API and excipients separately into a suitable container/plastic bags in Room 670. Check for lumps and screen the material if required using an 18 mesh screen. Fexofenadine Hydrochloride (R-1057) 15% Required 52.5 gm; Weighed gm. Avicel PH 102 (Microcrystalline cellulose) (R-1002) % Required gm; Weighed gm. Lactose 110M (Lactose monohydrate) (R-1012) 38.63% Required gm; Weighed gm. Ac-Di-Sol (Croscarmellose Na) (R-1016) 1.25% Required 4.38 gm; Weighed gm. Kollidon K-30 (Polyvinyl pyrollidone) (R-1013) 6.5% Note: 15% w/w solution in sterile water Required gm; Sprayed gm. Total weight of the blend (excluding the weight of the extragranular fraction) Label the container/bags - Fexofenadine blend Formulation A 2. Carefully transfer ALL the weighed materials into 8qt V- twin shell blender i.e blender UMB-00 check the fill volume once ALL the materials are transferred to the twin shell blender container. Fill volume % (visual inspection). If the fill volume is 40 to 70% of the blender - proceed to blending step (Step 6) 3. Blend for 5 min: Start Time: min; End Time: min

8 Effective: Page 8 of With a clean sampling thief (Conbar ) or spatula carefully collect 2 samples from each arm of the twin shell blender (approx 2 gm) into labeled scintillation vials (for Near infrared spectroscopy scans to test for blend uniformity). 5. Label the vial Blend + lot number 6. Note: Sample materials 3-5 cm from the surface of the powder bed with minimal disturbance to the powder bed. 7. Carefully transfer the contents of the twin shell blender into a suitable plastic bag. Note: Minimize the height of pouring to reduce segregation. 8. Label the plastic bag Fexo A blend + lot number 9. Double bag it and set it aside for Fluid bed granulation Weight of material being granulated gms. 10. Before granulation, follow area clearance steps For Fluid bed equipment set-up and operation, follow SOP Program Pyrobuttons and NIR process analyzer (please refer equipment/software manual for detail procedures) 13. Preheat Fluid bed to an air inlet temp of 50 0 C, make sure this temperature is maintained for 5 min., then charge Fexo A blend + Lot number into fluid bed

9 Effective: Page 9 of Before the granulation, record the following: Relative Humidity: (%) Temperature: ( 0 c) LOD Initial blend: (%) Initial wt of binder sol: gm Atomization pressure: psi Binder sol flow rate: gm/min Granulation start time: Pyrobutton data collection start time: NIR data collection start time: 15. During granulation increase the inlet air flow rate by 2 SCFM every 5 min. Record results in table below 16. Stop spraying the binder solution when the desired amount is added Amount of binder sol sprayed: 17. After binder solution spraying ends, lower the SCFM to 6 SCFM for the remaining of the time. ml 18. Save the NIR moisture data every 20 min

10 Effective: Page 10 of Record the following parameters every 5 min during granulation and drying. Time (min) Inlet air (SCFM) Inlet temp ( 0 c) Outlet temp ( 0 c) Product temp ( 0 c) 20. Sample approximately 1 gm of material every 5 min through the sample port to determine the moisture levels and record the following parameters. Time (min) NIR Probe ID LOD (%)

11 Effective: Page 11 of Stop the drying process when desired granule moisture content is reached. Limit: NMT 1% of starting moisture Final Moisture: (%) 22. Sieve the granules using Mesh # 18 and transferee the material into appropriate bag and label: Fexo A granules + lot number 23. Record the following parameters at the end of drying: Granulation end time: Pyrobutton data collection end time: NIR data collection end time: Final weight of granules: gm 24. Calculate yield (%) = gm 25. Read and save all the pyrobutton data

12 Effective: Page 12 of Weigh the following extragranular portion: Granules (Fexo A granules + lot no) 85% Final granulation total blend 200 g; 85% granules Required 170 gm; Weighed gm. Avicel PH 102 (Microcrystalline cellulose) (R-1002) 9% Required _ 18 _gm; Weighed gm. Klucel EXF (Hydroxypropyl cellulose) (R-1019) 5% Required _ 10 _gm; Weighed gm. Magnesium Stearate - Kosher Passover (Covidien) (R- 1017) 0.5% Required _ 1 _gm; Weighed gm. Aerosil 200 (Aerosilized silica) (R-1005) 0.5% Required _ 1 _gm; Weighed gm. 27. Sieve the extragranular excipients using Mesh # Carefully transfer ALL the weighed materials into 8qt V- twin shell blender i.e blender UMB Check the fill volume once ALL the materials are transferred to the twin shell blender container. Fill volume % (visual inspection). 30. Blend for 2 min: Start Time: min; End Time: min

13 Effective: Page 13 of Carefully transfer the contents of the twin shell blender into a suitable plastic bag. Note: Minimize the height of pouring to reduce segregation. 32. Label the plastic bag Blend for tableting: Fexo A + lot number 33. Set-up the tablet press with the hopper, feed frame and the force transducers (National instruments) attached to the computer system as described in the SOP-025. Pay careful attention to the safety notes outlined in the Operating procedures of SOP Ensure that the gap between the feed frame and the die table is paper thick (A regular A4 paper should be able to slide in and out between the die table and the feed frame) 35. Carefully pour the material (Blend for tableting: Fexo A + lot number) into the feed frame of the tablet press. 36. Manually operate/rotate the tablet press to ensure that the feed frame is evenly filled with the granules and flow well onto the die table and die cavity. 37. Continue the rotation to produce a couple of tablets - ensure that all the parts of the press are working (SOP- 025). Target weight of the tablets is 470 mg, however a range mg [Target weight = 470 mg]. 38. Power on the computer and the National Instruments chassis attached to the force transducers on the tablet press. Start the national instruments software and begin monitoring the compression forces on the tablet press (as described in SOP-025).

14 Effective: Page 14 of Turn on the tablet press, allow the machine to stabilize i.e. discard first 5 tablets and check the weight of the next 2 tablets. Adjust the height of the weight control cam to make mg tablets. 40. Using the transducers and software (National instruments) adjust the compression force to mv. 41. Throughout the collection time monitor and ensure that the compression force is within limits (Step 43). 42. Collect tablets until the end of production. Transfer these tablets into previously labeled containers Fexo A- Fexofenadine Hydrochloride USP 60 mg 43. At the end of the run perform cleaning according the SOP Post-Production Sampling, Material Transfer and Storage 11. Yield Calculations Granulation Yield Yield =100 x weight of granulation weight of powder (350 gm) Yield =

15 Effective: Page 15 of Production Comment Log Record any comments or observations from the production process. Initial and date each comment. Quality Assurance shall review, initial and date each comment or observation following production. Comment / Observation Step No QA Verified

16 Effective: Page 16 of Exception Log Record all Exceptions that occur during the production process. Quality Assurance shall review, classify, initial and date each entry following production, or as required. Planned Deviations and Nonconformances require a documented Nonconformance Report according to Nonconformances (SOP-005). Exception Documented Class (E, PD, NC) QA Verified E = Exception PD = Planned Deviation NC = Nonconformance

17 Effective: Page 17 of Post- Production Review The complete Post-Production has been reviewed for completeness and accuracy. All pages are complete and all entries conform to Good Documentation Practices. Name Signature Date Production Ravi Kona Quality Assurance Stephen W. Hoag 15. Quality Assurance Disposition The material produced through the execution of this shall be Dispositioned by QA according to Material Disposition and Status Labeling (SOP-010). The Disposition shall be recorded below. RELEASED Quantity (Units) CONDITIONAL RELEASE RESEARCH USE ONLY REJECTED (Include Comments) UMB assigned Use-By Date (MM/DD/YY or MM/YY) Comments Quantity (Units) Quantity (Units) Quantity (Units) Retest Expiration Stephen W. Hoag (Print) By - Quality Assurance Signature Date 16. Version Summary